Chapter 5- Genetic Disorders Flashcards
What is a common example of trinucleotide repeat mutation
Fragile X syndrome
What is the mutation in most autosomal dominant disorders
Loss of function mutation
What is an example of a urinary autosomal dominant disorder
Polycystic kidney disease
What is an example of GI autosomal dominant disorder
Familial polypoid coli
What is the largest category of Mendelian disorders
Autosomal recessive
What should you think about if there is an autosomal recessive disorder that is rare
Consanguinity
What is an example of an X-linked dominant disorder
Vitamin D resistant rickets
What antimalarial drug administered to someone with G6PD deficiency can lead to hemolytic anemia
Primaquine
What is the mutation in tay Sachs disease
Hexosaminidase
What is defective in Marfan syndrome
Fibrillin-1 (FBN-1 gene)
What type if murmur is most common with Marfan syndrome
Mitral regurgitation
What is the mainstay treatment for Marfan syndrome
Beta blockers
What is the most common type of Ehlers-danlos syndrome
Kyphoscoliosis
What is the gene defect in classic Ehlers-danlos syndrome
COL5A1, COL5A2
What is the clinical findings with classic Ehlers-danlos syndrome
Skin and joint hypermobility, atrophic scars, easy bruising
What are the clinical findings with hypermobility (III) Ehlers-danlos syndrome
Joint hypermobility, pain, dislocations
What is the defect in vascular (IV) Ehlers-danlos syndrome
COL3A1
What is the clinical findings associated with Ehlers-danlos syndrome vascular type (IV)
Thin skin, arterial or uterine rupture, brushing, small joint hyperextensibility
What is the defect seen with kyphoscoliosis Ehlers-danlos syndrome
Lysyl hydroxylase
What is the clinical findings associated with kyphoscoliosis Ehlers-danlos syndrome
Hypotonia, joint laxity, congenital scoliosis, ocular fragility
What is the defect with arthrochalasia Ehlers-danlos syndrome
COL1A1, COL1A2
What is the clinical findings associated with arthrocholasia Ehlers-danlos syndrome
Severe joint hypermobility, skin changes (Mild), scoliosis, bruising
What is the defect with dermatosparaxis Ehlers-danlos syndrome
Procollagen N-peptidase
What are the clinical findings associated with dermatosparaxis Ehlers-danlos syndrome
Severe skin fragility, cutis laxa, bruising
Describe class 2 mutation in gene encoding receptor for LDL
Receptor proteins accumulate in ER and cannot be transported to golgi complex
Describe class 1 mutation in gene encoding receptor for LDL
Complete failure of synthesis of receptor protein
Describe class 3 mutation in gene encoding receptor for LDL
LDL binding domain of the receptor affected
Describe class 4 mutation in gene encoding receptor for LDL
Bound LDL is not internalized (encode proteins that are synthesized and transported to the cell surface efficiently, but fault to localize in coated pits_
Describe class 5 mutation in gene encoding receptor for LDL
Ph dependent dissociation of receptor and bound LDL fails
Who is Tay Sachs particularly common in
Jews
What dominates the picture of Tay Sachs disease
Involvement of neurons in CNS and ANS and retinal
What lysosomal storage disorder is associated with cherry red spot macula
Tay Sachs
What is deficient in sandhoff
Hexosaminidase beta subunit
What type of mutation is in Norman pick disease type A
Missense mutation
What should you think of with zebra bodies
Type A Neiman pick disease
What is the clinical picture with Type A Neimann-pick disease
Progressive failure to thrive, vomiting, fever, generalized lymphadenopathy
What is responsible for 95% of cases of Type C Niemann pick disease
NPC1
What is the common presentation of type C Niemann pick disease
Marked ataxia, vertical supranuclear gaze palsy, dystopia, dysarthria & psychomotor regression; may have neonatal hepatitis
What is the issue with gaucher disease
Mutation in gene encoding glucocerebrosidase
What is the most common lysosomal storage disorder
Gaucher disease
Where does the glucocerebroside in gaucher disease accumulate
Phacoytes
What are some common findings with type 1 gaucher disease
Predilection for Jews; pancytopenia, thrombocytopenia (secondary to hypersplenomegaly); pathology fractures or bone pain
What is the only mucopolyaccharidoses that is NOT AR
Hunter syndrome (X-linked recessive)
What does hurler syndrome result from deficiency of
Alpha-1 iduronidase
What disease is associated with deficiency of muscle phosphorylase
McCardle disease
What are the clinical features associated with velocardiofacial syndrome
Facial dysmorphism, cleft palate, CVS anomalies, learning disabilities
What psychiatric disorder are individuals with DiGeorge and velocardiofacial syndrome more likely to develop
Schizophrenia
What are the 2 most common things seen in Klinefelter syndrome
Reduced spermatogenesis and male infertility
What is the most important cause of increased mortality in kids with Turner syndrome
Cardiovascular disease
What is the protein issue with spinobulbar muscular atrophy (Kennedy syndrome)
Androgen receptor
What is the issue with dentarubral-pallidoluysian atrophy (Haw river syndrome)
Atrophin-1
What is the most common phenotypic finding with fragile X syndrome
Macro-orchidism
What repeats are increased in fragile X syndrome
CGG
What is fragile X tremor/ataxia characterized by
Intention tremor, cerebellar ataxia and may progress to Parkinsonism
What is the prototype of mitochondrial inheritance disorder
Leber hereditary optic neuropathy
What organs does leber hereditary optic neuropathy have the most effect
Those dependent on ox phos (CNS, skeletal muscle, cardiac muscle, liver and kidney)
What is deleted in angelman syndrome
Maternally derived chromosome 15
What is deleted in prader willi
Paternally derived Chromosome 15
What gene is implicated in angelman syndrome
UBE3A (ubiquitin ligase)
When is pyrosequencing most often used
When testing for particular sequence variant
She is southern blotting most useful
In detection of certain large trinucleotide expansion diseases
When are SNPs used
In linkage analysis for identifying haplotypes associated with disease
When are minisatellites and microsatellites routinely used
For paternity tests and criminal investigations
What is deficient in Von Gierke?
Glucose-6-phosphatase
What is deficient in Pompe?
acid maltase (a-glucosidase)
Diseases at increased risk with Down’s Syndrome
- Acute leukemia
- Alzheimers
- Congenital heart defects
- Infections
